药物的人体内肝脏代谢清除率的体外预测  

In vitro prediction of in vivo hepatic metabolic clearance of drugs in human

作　　者：李海燕[1] 孙进[1] 何仲贵[1] 

机构地区：[1]沈阳药科大学药学院药物制剂教研室,辽宁沈阳110016

出　　处：《中国新药与临床杂志》2007年第9期702-707,共6页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：在药物开发初期,就将药动学性质不佳的新化学实体剔除出去具有十分重要的意义。通过人体内肝脏代谢清除率的体外预测,可以淘汰那些可能从体内迅速被清除的化合物,并可以建立口服生物利用度的预测模型,以指导临床剂量的确定。本文以肝微粒体和肝细胞为模型,阐述药物的人体内肝脏代谢清除率的体外预测过程,并讨论药物的蛋白结合对预测的影响。It is of great importance to identify the new chemical entity （NCE） with poor pharmacokinetic properties early in drug discovery pipeline. In vitro prediction of in vivo hepatic metabolic clearance of compounds in human can be used to screen those compounds that are likely to be eliminated too quickly from the body and, therefore, to establish models for predicting oral bioavailability and to direct the clinical dosage regimen. This review presents a strategy to achieve the prediction of in vivo human hepatic clearance of drugs from in vitro systems such as hepatic microsomes and hepatocytes. The potential role of plasma and matrix protein binding in accurate clearance prediction is also discussed.

关 键 词：代谢清除率 预测 蛋白质结合 药物开发 

分 类 号：R945[医药卫生—微生物与生化药学]